This invention relates to novel ester derivatives of prostaglandin E.sub.1 (hereinafter identified as "PGE.sub.1 "), 15-alkyl-PGE.sub.1, 15(R)-15-alkyl-PGE.sub.1, and their racemic forms, and to processes for producing them.
PGE.sub.1 is represented by the formula: ##SPC1##
A systematic name for PGE.sub.1 is 7-{3.alpha.-hydroxy-2.beta.-[(3S)-3-hydroxy-trans-1-octenyl]-5-oxo-1.alpha .-cyclopentyl}-heptanoic acid. PGE.sub.1 is known to be useful for a variety of pharmacological and medical purposes, for example labor induction and abortion in pregnant animals, including humans, menstrual regulation in both pregnant and non-pregnant animals, including humans, reduction and control of gastric secretion, and as a hypotensive agent to reduce blood pressure in mammals, including humans. See Bergstrom et al., Pharmacol. Rev. 20, 1 (1968) and references cited therein. As to racemic PGE.sub.1, see for example W. P. Schneider et al., J. Am. Chem. Soc. 91, 5372 (1969).
The 15-alkyl-PGE.sub.1 analog and its 15(R) epimer are represented by the formula: ##SPC2## wherein Y' is ##EQU1## following the usual convention wherein broken line attachment of hydroxy to the side chain at carbon 15 indicates the natural or S configuration and solid line attachment of hydroxy indicates the epi or R configuration. See for example Nugteren et al., Nature 212, 38 (1966) and Cahn, J. Chem. Ed. 41, 116 (1964). The 15-alkyl- and 15(R)-15-alkyl-PGE.sub.1 analogs in their optically active and racemic forms are known. See for example U.S. Pat. No. 3,728,382. These analogs are also useful for the above-described pharmacological purposes.
Esters of the above compounds are known, wherein the hydrogen atom of the carboxyl group is replaced by a hydrocarbyl or substituted hydrocarbyl group. Among these are the methyl ester of PGE.sub.1 (B. Samuelsson, J. Biol. Chem. 238, 3229 (1963)), (see also U.S. Pat. No. 3,069,322), the methyl esters of 15-methyl-PGE.sub.1 and dl-15-methyl-PGE.sub.1 (G. L. Bundy et al., Ann. N.Y. Acad. Sci. 180, 76 (1971)), the ethyl ester of PGE.sub.1 (R. Ryhage et al., Biochem. Biophys. Res. Commun. 19, 279 (1965)), and the octafluoro-1-pentyl ester of PGE.sub.1 (Belgian Patent 775,106, Derwent Farmdoc No. 33705T).